Breast NeoplasmsPhase 1NCT00146172

Study Evaluating HKI-272 in Tumors

A Phase 1 study testing neratinib in people with Breast Neoplasms, run by Puma Biotechnology, Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to evaluate the safety and tolerability as well as find the maximum tolerated dose (MTD) for HKI-272. In addition, this study will examine the effects of the study drug on your tumor, and how your body uses and eliminates HKI-272. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Breast Neoplasms
What is being tested?: neratinib
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 73 participants
Where: 5 sitesUnited States
Study dates: Nov 2003to Jan 2007
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Her2/neu or Her1/EGFR positive cancer
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)

Who cannot join

Prior treatment with anthracyclines with a cumulative dose of doxorubicin or equivalent of greater than 300 mg/m^2
Patients with significant cardiac risk factors
Active central nervous system metastasis

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
The Cleveland Clinic Foundation Taussig Cancer Center
Cleveland, Ohio, 44195
The Sarah Cannon Cancer Center
Nashville, Tennessee, 37203
Washington University School of Medicine
St Louis, Missouri, 63110
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612

Other trials in United States

About this study

Official title: An Ascending Single and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HKI-272 Administered Orally to Subjects With HER-2/NEU or HER-1/EGFR-Positive Tumors

Conditions: Breast Neoplasms
Being tested: neratinib
Keywords: Tumors, Neratinib, HKI-272, Nerlynx
Medical subject headings: Breast Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

neratinibDrug
HKI-272

Study groups in NCT00146172
Study group	Role	What they receive
Neratinib 40 mg	Experimental	Not described Receives: Drug: neratinib
Neratinib 80 mg	Experimental	Not described Receives: Drug: neratinib
Neratinib 120 mg	Experimental	Not described Receives: Drug: neratinib
Neratinib 180 mg	Experimental	Not described Receives: Drug: neratinib
Neratinib 240 mg	Experimental	Not described Receives: Drug: neratinib
Neratinib 320 mg	Experimental	Not described Receives: Drug: neratinib
Neratinib 400 mg	Experimental	Not described Receives: Drug: neratinib
Neratinib 320 mg MTD	Experimental	Not described Receives: Drug: neratinib

What is being measured

The primary outcome is the main question the study is designed to answer.

Dose Limiting Toxicity (DLT)
DLT is defined as any neratinib-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) common terminology criteria (CTC) for AEs version 3.0. DLTs were assessed from the first single dose to 14 days of continuous daily administration.
Measured: From first dose date to day 14
Maximum Tolerated Dose (MTD)
If 2 or more, of 3 to 6 subjects, at a dose level had an neratinib-related dose limiting toxicity (DLT) by day 14 of continuous daily dose administration, dose escalation stopped and the prior dose level was considered the MTD.
Measured: From first dose date to day 14

Secondary outcomes (5)

Number of Participants With Best Overall Response
Best Overall response by tumor type, evaluable population per Response Evaluation Criteria In Solid Tumors Criteria v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in sum of the longest diameter (LD) of target lesions in reference to baseline sum of LD of target lesions; Progressive Disease (PD), >=20% increase in sum of LD of target lesions, taking as reference the smallest sum of recorded LD of target lesions since treatment started or appearance of 1 or more new lesions; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD of target lesions since the treatment start. The best overall response was the best response recorded from start of treatment until PD/recurrence. In general, the subject's best response assignment depended on achievement of both measurement and confirmation criteria.
Measured: From first dose date to progression or last tumor assessment, up to 39 weeks.
Duration of Response
Duration of response of responders (PR+) by Kaplan-Meier estimate
Measured: From start date of response to first PD, up to 39 weeks.
Progression Free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: From first dose date to progression or death, up to 39 weeks.
Objective Response Rate
Patients with PR or higher responses, evaluable population
Measured: From first dose date to progression/death or last assessment, up to 39 weeks
Clinical Benefit Rate
Patients with PR or higher responses or SD>=24 weeks, evaluable population
Measured: From first dose date to progression/death or last assessment, up to 39 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2003Jan 2007

First posted5 Sep 2005 (estimated)
Study startNov 2003
Primary completionJan 2007
Study completionJan 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: This trial was an open-label, phase 1, ascending single and multiple oral dose study of HKI-272 administered to subjects with erbB-2- or erbB-1-positive tumors. Each subject participated in only 1 dose group and received a single dose of test article, followed by a 1-week observation period, and then received the test article administered once daily by mouth for up to 6 months (6 cycles). Daily dose administration could continue beyond 6 cycles at the same dose level if HKI-272 was well tolerated and there was no evidence of progressive disease.
Masking: None (open label)
Enrolment: 73 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00146172
Sponsor's protocol ID: 3144A1-102
Status last verified: Aug 2018
First submitted: 2 Sep 2005
Last updated: 17 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 3
S1501 Dual Observational and Randomized Cohort Study of Patients With Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity
Cardiotoxicity, HER2/Neu Positive
Active, not recruitingPhase 3
ExclUsive endocRine Therapy Or Radiation theraPy for Women Aged ≥70 Years Early Stage Breast Cancer
Breast Cancer
RecruitingPhase 1/2
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
Liposarcoma, Prostate Cancer
RecruitingObservational study
Avera Cancer Sequencing and Analytics Protocol (ASAP)
Cancer, Cancer Diagnosis

All Breast Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Ascending Single and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HKI-272 Administered Orally to Subjects With HER-2/NEU or HER-1/EGFR-Positive Tumors
ClinicalTrials.gov ID: NCT00146172
Acronym / sponsor ID: 3144A1-102
Conditions: Breast Neoplasms
Keywords: Tumors, Neratinib, HKI-272, Nerlynx
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 73 participants (actual)
Lead sponsor: Puma Biotechnology, Inc.Industry (pharma, biotech, devices)
Study start: Nov 2003 (actual)
Primary completion: Jan 2007 (actual)
Study completion: Jan 2007 (actual)
First posted: 5 Sep 2005 (estimated)
Results: Posted 13 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 8
Model description: This trial was an open-label, phase 1, ascending single and multiple oral dose study of HKI-272 administered to subjects with erbB-2- or erbB-1-positive tumors. Each subject participated in only 1 dose group and received a single dose of test article, followed by a 1-week observation period, and then received the test article administered once daily by mouth for up to 6 months (6 cycles). Daily dose administration could continue beyond 6 cycles at the same dose level if HKI-272 was well tolerated and there was no evidence of progressive disease.

Arm	Type	Receives
Neratinib 40 mg	Experimental	Drug: neratinib
Neratinib 80 mg	Experimental	Drug: neratinib
Neratinib 120 mg	Experimental	Drug: neratinib
Neratinib 180 mg	Experimental	Drug: neratinib
Neratinib 240 mg	Experimental	Drug: neratinib
Neratinib 320 mg	Experimental	Drug: neratinib
Neratinib 400 mg	Experimental	Drug: neratinib
Neratinib 320 mg MTD	Experimental	Drug: neratinib

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Her2/neu or Her1/EGFR positive cancer
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)

Key exclusion criteria (3 listed)

Prior treatment with anthracyclines with a cumulative dose of doxorubicin or equivalent of greater than 300 mg/m^2
Patients with significant cardiac risk factors
Active central nervous system metastasis

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
neratinibHKI-272	Drug	Neratinib 120 mg, Neratinib 180 mg, Neratinib 240 mg, Neratinib 320 mg, Neratinib 320 mg MTD, Neratinib 40 mg, Neratinib 400 mg, Neratinib 80 mg

Primary outcome

Dose Limiting Toxicity (DLT)
Time frame: From first dose date to day 14
DLT is defined as any neratinib-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) common terminology criteria (CTC) for AEs version 3.0. DLTs were assessed from the first single dose to 14 days of continuous daily administration.
Maximum Tolerated Dose (MTD)
Time frame: From first dose date to day 14
If 2 or more, of 3 to 6 subjects, at a dose level had an neratinib-related dose limiting toxicity (DLT) by day 14 of continuous daily dose administration, dose escalation stopped and the prior dose level was considered the MTD.

5 secondary outcomes

Number of Participants With Best Overall Response
Time frame: From first dose date to progression or last tumor assessment, up to 39 weeks.
Duration of Response
Time frame: From start date of response to first PD, up to 39 weeks.
Progression Free Survival
Time frame: From first dose date to progression or death, up to 39 weeks.
Objective Response Rate
Time frame: From first dose date to progression/death or last assessment, up to 39 weeks
Clinical Benefit Rate
Time frame: From first dose date to progression/death or last assessment, up to 39 weeks.

Results and safety

Results posted to the registry on 13 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Neratinib 40 mg	3	0
Neratinib 80 mg	4	0
Neratinib 120 mg	4	0
Neratinib 180 mg	6	0
Neratinib 240 mg	3	0
Neratinib 320 mg	7	0
Neratinib 400 mg	6	0
Neratinib MTD	40	0

Primary outcome: Dose Limiting Toxicity (DLT)

Time frame: From first dose date to day 14. Count of participants. Unit: Participants

Measure	Neratinib 40 mg n = 3	Neratinib 80 mg n = 4	Neratinib 120 mg n = 4	Neratinib 180 mg n = 6	Neratinib 240 mg n = 3	Neratinib 320 mg n = 7	Neratinib 400 mg n = 6
Value	0	0	0	1	0	0	4

Population analysed: Subjects in the dosing groups 40 mg through 400 mg, excluding the selection of MTD.

Primary outcome: Maximum Tolerated Dose (MTD)

Time frame: From first dose date to day 14. Number. Unit: mg

Measure	Neratinib 320 mg n = 33
Value	320

Population analysed: All patients receiving neratinib in the dose escalation part of the study.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose through 28 days after last dose, up to 39 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Neratinib 40 mg	3 of 3 (100%)	3 of 3 (100%)	Not reported
Neratinib 80 mg	1 of 4 (25%)	4 of 4 (100%)	Not reported
Neratinib 120 mg	1 of 4 (25%)	4 of 4 (100%)	Not reported
Neratinib 180 mg	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
Neratinib 240 mg	0 of 3 (0%)	3 of 3 (100%)	Not reported
Neratinib 320 mg	4 of 7 (57.1%)	7 of 7 (100%)	Not reported
Neratinib 400 mg	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
Neratinib MTD	14 of 39 (35.9%)	39 of 39 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Breast Neoplasms

RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 3
S1501 Dual Observational and Randomized Cohort Study of Patients With Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity
Cardiotoxicity, HER2/Neu Positive
Active, not recruitingPhase 3
ExclUsive endocRine Therapy Or Radiation theraPy for Women Aged ≥70 Years Early Stage Breast Cancer
Breast Cancer
RecruitingPhase 1/2
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
Liposarcoma, Prostate Cancer
RecruitingObservational study
Avera Cancer Sequencing and Analytics Protocol (ASAP)
Cancer, Cancer Diagnosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Puma study director

Biotechnology

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing neratinib in people with Breast Neoplasms, run by Puma Biotechnology, Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (DLT) (time frame: From first dose date to day 14). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00146172.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2018; AzTrials last refreshed its copy on 29 Oct 2026.